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Background: Trials of cancer screening present results in terms of deaths prevented, but metastasis is also a key endpoint that screening seeks to prevent. We developed a framework for projecting overall (de novo and progressive) metastases prevented in a screening trial using prostate cancer screening as a case study. Methods: Mechanistic simulation model in which screening shifts a fraction of cases that would be metastatic at diagnosis to being non-metastatic. This shift increases the incidence of non-overdiagnosed, organ-confined cases. We use estimates of the risk of metastatic progression for these cases to project how many progress to metastasis after diagnosis and tally the projected de novo and progressive metastatic cases with and without screening. We use data on stage shift from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and data on the risk of metastatic progression from the Scandinavian Prostate Cancer Group-4 trial. We estimate the relative risk and absolute risk reductions in metastatic disease at diagnosis and compare these with reductions in overall metastases. Results: Assuming no effect of screening beyond initial stage shift at diagnosis, the model projects a 43% reduction in metastasis at diagnosis but a 22% reduction in the cumulative probability of metastasis over 12 years in favor of screening. These results are consistent with the empirical findings from the ERSPC. Conclusion: Any reduction in metastatic disease at diagnosis under screening is likely to be an overly optimistic predictor of the impact of screening on overall metastasis and disease-specific mortality. [ABSTRACT FROM AUTHOR]

Rye consumption has shown beneficial effects on prostate cancer tumors, as indicated by slower initial tumor growth in animal models and lowering of prostate-specific antigen (PSA) in humans. This study evaluated the effects of whole grain/bran rye consumption on low-grade inflammation and endothelial function biomarkers in men with prostate cancer. Seventeen men with untreated, low-grade prostate cancer consumed 485 g rye whole grain and bran products (RP) per day or refined wheat products with added cellulose (WP) in a randomized crossover design. Fasting blood samples were taken before and after 2, 4, and 6 weeks of treatment. Concentrations of tumor nuclear factor-receptor 2 (TNF-R2), e-selectin, and endostatin were significantly lower after consumption of the RP diet compared with WP (p < 0.05). Cathepsin S concentration was positively correlated to TNF-R2 and endostatin concentrations across all occasions. Strong correlations were consistently found between intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and between interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA). No effect of intervention was found in 92 inflammation-related protein biomarkers measured in a proximity extension assay. RP diet lowered TNF-R2, e-selectin, and endostatin, compared with WP in men with prostate cancer. These effects were accompanied by a reduction in PSA. [ABSTRACT FROM AUTHOR]

Dairy intake has been associated with increased risk of advanced prostate cancer. Two US cohort studies reported increased prostate cancer-specific mortality with increased high-fat milk intake. We examined whether dairy and related nutrient intake were associated with prostate cancer progression in a Swedish patient population with high dairy consumption. We prospectively followed 525 men with newly diagnosed prostate cancer (diagnosed 1989-1994). We identified and confirmed deaths through February 2011 ( n = 222 prostate cancer-specific, n = 268 from other causes). Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between food or nutrient intake and prostate cancer-specific death. On average, patients consumed 5.0 servings/day of total dairy products at diagnosis. In the whole population, high-fat milk intake was not associated with prostate cancer-specific death (95% CI: 0.78, 2.10; p-trend = 0.32; multivariate-adjusted model). However, among patients diagnosed with localized prostate cancer, compared to men who consumed <1 servings/day of high-fat milk, those who drank ≥3 servings/day had an increased hazard of prostate cancer mortality (HR = 6.10; 95% CI: 2.14, 17.37; p-trend = 0.004; multivariate-adjusted model). Low-fat milk intake was associated with a borderline reduction in prostate cancer death among patients with localized prostate cancer. These associations were not observed among patients diagnosed with advanced stage prostate cancer. Our data suggest a positive association between high-fat milk intake and prostate cancer progression among patients diagnosed with localized prostate cancer. Further studies are warranted to investigate this association and elucidate the mechanisms by which high-fat milk intake may promote prostate cancer progression. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) are highly persistent environmental pollutants and are undesirable components of our daily food. PCBs are classified as human carcinogens, but the evidence for prostate cancer is limited and available data are inconsistent. We explored the link between non-dioxin-like PCB and grade of prostate cancer in a prospective cohort as well as in cell experiments. A population-based cohort of 32 496 Swedish men aged 45-79 years was followed prospectively through 1998-2011, to assess the association between validated estimates of dietary PCB exposure and incidence of prostate cancer by grade (2789 cases, whereof 1276 low grade, 756 intermediate grade, 450 high grade) and prostate cancer mortality (357 fatal cases). In addition, we investigated a non-dioxin-like PCB153-induced cell invasion and related markers in normal prostate stem cells (WPE-stem) and in three different prostate cancer cell lines (PC3, DU145 and 22RV1) at exposure levels relevant to humans. After multivariable-adjustment, dietary PCB exposure was positively associated with high-grade prostate cancer, relative risk (RR) 1.35 [95% confidence interval (CI): 1.03-1.76] and with fatal prostate cancer, RR 1.43 (95% CI: 1.05-1.95), comparing the highest tertile with the lowest. We observed no association with low or intermediate grade of prostate cancer. Cell invasion and related markers, including MMP9, MMP2, Slug and Snail, were significantly increased in human prostate cancer cells as well as in prostate stem cells after exposure to PCB153. Our findings both from the observational and experimental studies suggest a role of non-dioxin-like PCB153 in the development of high-grade and fatal prostate cancer. [ABSTRACT FROM AUTHOR]

In 1987, the first Regional Prostate Cancer Register was set up in the South-East health-care region of Sweden. Other health-care regions joined and since 1998 virtually all prostate cancer (PCa) cases are registered in the National Prostate Cancer Register (NPCR) of Sweden to provide data for quality assurance, bench marking and clinical research. NPCR includes data on tumour stage, Gleason score, serum level of prostate-specific antigen (PSA) and primary treatment. In 2008, the NPCR was linked to a number of other population-based registers by use of the personal identity number. This database named Prostate Cancer data Base Sweden (PCBaSe) has now been extended with more cases, longer follow-up and a selection of two control series of men free of PCa at the time of sampling, as well as information on brothers of men diagnosed with PCa, resulting in PCBaSe 2.0. This extension allows for studies with case–control, cohort or longitudinal case-only design on aetiological factors, pharmaceutical prescriptions and assessment of long-term outcomes. The NPCR covers >96% of all incident PCa cases registered by the Swedish Cancer Register, which has an underreporting of <3.7%. The NPCR is used to assess trends in incidence, treatment and outcome of men with PCa. Since the national registers linked to PCBaSe are complete, studies from PCBaSe 2.0 are truly population based. [ABSTRACT FROM AUTHOR]

Objective. This study aimed to develop a probabilistic decision support model to calculate the lifetime incremental cost-effectiveness ratio (ICER) between radical prostatectomy and watchful waiting for different patient groups. Material and methods. A randomized trial (SPCG-4) provided most data for this study. Data on survival, costs and quality of life were inputs in a decision analysis, and a decision support model was developed. The model can generate cost-effectiveness information on subgroups of patients with different characteristics. Results. Age was the most important independent factor explaining cost-effectiveness. The cost-effectiveness value varied from 21 026 Swedish kronor (SEK) to 858 703 SEK for those aged 65 to 75 years, depending on Gleason scores and prostate-specific antigen (PSA) values. Information from the decision support model can support decision makers in judging whether or not radical prostatectomy (RP) should be used to treat a specific patient group. Conclusions. The cost-effectiveness ratio for RP varies with age, Gleason scores, and PSA values. Assuming a threshold value of 200 000 SEK per quality-adjusted life-year (QALY) gained, for patients aged ≤70 years the treatment was always cost-effective, except at age 70, Gleason 0-4 and PSA ≤10. Using the same threshold value at age 75, Gleason 7-9 (regardless of PSA) and Gleason 5-6 (with PSA >20) were cost-effective. Hence, RP was not perceived to be cost-effective in men aged 75 years with low Gleason and low PSA. Higher threshold values for patients with clinically localized prostate cancer could be discussed. [ABSTRACT FROM AUTHOR]

Prostate cancer (PC) is the most common cancer in the Western world and the second most important cancer causing male deaths, after lung cancer, in the United States and Britain. Lifestyle and dietary changes are recommended for men diagnosed with early-stage PC. It has been shown that a diet rich in whole grain (WG) rye reduces the progression of early-stage PC, but the underlying mechanism is not clear. This study sought to identify changes in the metabolic signature of plasma in patients with early-stage PC following intervention with a diet rich in WG rye and rye bran product (RP) compared with refined white wheat product (WP) as a tool for mechanistic investigation of the beneficial health effects of RP on PC progression. Seventeen PC patients received 485 g RP or WP in a randomized, controlled, crossover design during a period of 6 wk with a 2-wk washout period. At the end of each intervention period, plasma was collected after fasting and used for ¹H NMR-based metabolomics. Multilevel partial least squares discriminant analysis was used for paired comparisons of multivariate data. A metabolomics analysis of plasma showed an increase in 5 metabolites, including 3-hydroxybutyric acid, acetone, betaine, N,N-dimethylglycine, and dimethyl sulfone, after RP. To understand these metabolic changes, fasting plasma homocysteine, leptin, adiponectin, and glucagon were measured separately. The plasma homocysteine concentration was lower (P = 0.017) and that of leptin tended to be lower (P = 0.07) after RP intake compared to WP intake. The increase in plasma 3-hydroxybutyric acid and acetone after RP suggests a shift in energy metabolism from anabolic to catabolic status, which could explain some of the beneficial health effects of WG rye, i.e., reduction in prostate-specific antigen and reduced 24-h insulin secretion. In addition, the increase in betaine and N,N-dimethylglycine and the decrease in homocysteine show a favorable shift in homocysteine metabolism after RP intake. [ABSTRACT FROM AUTHOR]

Objective. The cost of radical prostatectomy (RP) compared to watchful waiting (WW) has never been estimated in a randomized trial. The goal of this study was to estimate long-term total costs per patient associated with RP and WW arising from inpatient and outpatient hospital care. Material and methods. This investigation used the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial, comparing RP to WW, and included data from 212 participants living in two counties in Sweden from 1989 to 1999 (105 randomized to WW and 107 to RP). All costs were included from randomization date until death or end of follow-up in July 2007. Resource use arising from inpatient and outpatient hospital costs was measured in physical units and multiplied by a unit cost to come up with a total cost per patient. Results. During a median follow-up of 12 years, the overall cost in the RP group was 34% higher ( p < 0.01) than in the WW group, corresponding to €€6123 in Sweden. The difference was driven almost exclusively by the cost of the surgical procedure. The cost difference between RP and WW was two times higher among men with low (2--6) than among those with high (7--10) Gleason score. Conclusion. In this economic evaluation of RP versus WW of localized prostate cancer in a randomized study, RP was associated with 34% higher costs. This difference, attributed exclusively to the cost of the RP procedure, was not overcome during extended follow-up. [ABSTRACT FROM AUTHOR]

Objective. To investigate the effects of prostate-specific antigen (PSA) testing of men without clinical signs of prostate cancer on the incidence of prostate cancer in Sweden. Material and methods. Information on the cause of diagnosis, tumour characteristics and primary treatment for patients diagnosed with prostate cancer between January 1999 and December 2007 was extracted from the National Prostate Cancer Register of Sweden. This register includes data for 95% of Swedish prostate cancer cases. Results. The total age-standardized annual incidence of prostate cancer per 100 000 men increased from 187 in 1999 to 233 in 2004, but decreased thereafter to 196 in 2007. The incidence of asymptomatic cases also peaked in 2004 (at 62 per 100 000 men), but varied six-fold between different counties in that year (16-98 per 100 000 men). Asymptomatic cases ( n = 17 143) constituted 15% of all new cases in 2000 and 30% in 2007. Almost as many cases were diagnosed in stage T1c in men with symptoms, usually from the lower urinary tract. Together these two groups constituted 29% of all new cases in 2000 and 52% in 2007. It was estimated that at least one-third of all Swedish men aged 50-75 years had a PSA test between 2000 and 2007. Conclusions. Even though screening for prostate cancer is not recommended in Sweden, PSA testing of men without clinical signs of prostate cancer is common. The effects on the Swedish incidence of prostate cancer were similar to those reported from the USA. [ABSTRACT FROM AUTHOR]

Rye whole grain and bran intake has shown beneficial effects on prostate cancer progression in animal models, including lower tumor take rates, smaller tumor volumes, and reduced prostate specific antigen (PSA) concentrations. A human pilot study showed increased apoptosis after consumption of rye bran bread. In this study, we investigated the effect of high intake of rye whole grain and bran on prostate cancer progression as assessed by PSA concentration in men diagnosed with prostate cancer. Seventeen participants were provided with 485 g rye whole grain and bran products (RP) or refined wheat products with added cellulose (WP), corresponding to --50% of daily energy intake, in a randomized controlled, crossover design. Blood samples were taken from fasting men before and after 2, 4, and 6 wk of treatment and 24-h urine samples were collected before the first intervention period and after treatment. Plasma total PSA concentrations were lower after treatment with RP compared with WP, with a mean treatment effect of -14% (P= 0.04). Additionally, fasting plasma insulin and 24-h urinary C- peptide excretion were lower after treatment with R P compared with WP (P< 0.01 and P= 0.01, respectively). Daily excretion of 5 lignans was higherafter the RPtreatmentthan after the WPtreatment (P< 0.001). We conclude thatwhole grain and bran from rye resulted in significantly lower plasma PSA compared with a cellulose-supplemented refined wheat diet in patients with prostate cancer. The effect may be related to inhibition of prostate cancer progression caused by decreased exposure to insulin, as indicated by plasma insulin and urinary C-peptide excretion. [ABSTRACT FROM AUTHOR]

Background: Treatment for localized prostate cancer remains controversial. To our knowledge, there are no outcome studies from contemporary population-based cohorts that include data on stage, Gleason score, and serum levels of prostate-specific antigen (PSA). [ABSTRACT FROM PUBLISHER]

Background Stressful life events have been shown to be associated with altered risk of various health consequences. The aim of the present study was to investigate whether the emotional stress evoked by a prostate cancer diagnosis increases the immediate risks of cardiovascular events and suicide. Methods and Findings We conducted a prospective cohort study by following all men in Sweden who were 30 y or older (n = 4,305,358) for a diagnosis of prostate cancer (n = 168,584) and their subsequent occurrence of cardiovascular events and suicide between January 1, 1961 and December 31, 2004. We used Poisson regression models to calculate relative risks (RRs) and 95% confidence intervals (CIs) of cardiovascular events and suicide among men who had prostate cancer diagnosed within 1 y to men without any cancer diagnosis. The risks of cardiovascular events and suicide were elevated during the first year after prostate cancer diagnosis, particularly during the first week. Before 1987, the RR of fatal cardiovascular events was 11.2 (95% CI 10.4-12.1) during the first week and 1.9 (95% CI 1.9-2.0) during the first year after diagnosis. From 1987, the RR for cardiovascular events, nonfatal and fatal combined, was 2.8 (95% CI 2.5-3.2) during the first week and 1.3 (95% CI 1.3-1.3) during the first year after diagnosis. While the RR of cardiovascular events declined, the RR of suicide was stable over the entire study period: 8.4 (95% CI 1.9-22.7) during the first week and 2.6 (95% CI 2.1-3.0) during the first year after diagnosis. Men 54 y or younger at cancer diagnosis demonstrated the highest RRs of both cardiovascular events and suicide. A limitation of the present study is the lack of tumor stage data, which precluded possibilities of investigating the potential impact of the disease severity on the relationship between a recent diagnosis of prostate cancer and the risks of cardiovascular events and suicide. In addition, we cannot exclude residual confounding as a possible explanation. Conclusions Men newly diagnosed with prostate cancer are at increased risks for cardiovascular events and suicide. Future studies with detailed disease characteristic data are warranted. [ABSTRACT FROM AUTHOR]

Objective. The incidence of prostate cancer in Sweden is increasing rapidly, as is treatment with curative intent. Radical prostatectomy (RP) is currently commonly performed, either within or outside large high-volume centres. The aim of this study was to assess the 30-day mortality rate after RP in Sweden. Material and methods. In this nationwide population-based study, all men diagnosed with localized prostate cancer (≤70 years, clinical stadium T1–2, prostate-specific antigen <20 ng/ml) who underwent RP in Sweden between 1997 and 2002 were identified through the National Prostate Cancer Register (NPCR). Mortality within 30 days of RP was analysed through linkage between the follow-up study of the NPCR and the Regional Population Registers. The cause of death in the death certificates were compared with data from the hospitals concerned. To validate the results, a record linkage between the Inpatient Register and the National Population Register was also performed. Results. The number of RPs performed increased over time. Among 3700 RPs performed, four deaths occurred during the first 30 days, yielding a 0.11% 30-day mortality rate. These deaths occurred at three different types of hospital and were all probably related to the RP. Conclusion. This study provides further evidence that RP is a procedure with very low perioperative mortality even when performed outside high-volume centres. [ABSTRACT FROM AUTHOR]

Objective. To construct a database for clinical epidemiological prostate cancer research based on linkages between the National Prostate Cancer Register (NPCR) of Sweden, a population-based, nationwide quality database, and other nationwide registries. Material and methods. By use of the individually unique Swedish Personal Identity Number, the NPCR was linked to the Swedish Cancer Registry, the Cause of Death Register, the Prescribed Drug Register, the National Patient Register and the Acute Myocardial Infarction Register, all held at the Centre for Epidemiology at the National Board of Health and Welfare, and the Register of the Total Population, the Longitudinal Integration Database for Health Insurance and Labor Market Studies and the Multi-Generation Register, held at Statistics Sweden, and to the Swedish Hernia Register. Results. Record linkages between the NPCR and the Swedish Cancer Registry, the Cause of Death Register and the Register of the Total Population generated a database, named PCBaSe Sweden, including 80 079 prostate cancer cases, diagnosed between 1 January 1996 and 31 December 2006. Record linkage between PCBaSe Sweden and the Prescribed Drug Register generated 59 721 unique matches and linkage to the Acute Myocardial Infarction Register resulted in 11 459 matches. Conclusion. PCBaSe Sweden is a newly created and unique database with over 80 000 cases of prostate cancer with comprehensive data on inpatient and outpatient care, patterns of use of prescribed drugs and socioeconomic and familial factors. Many topics in clinical prostate cancer epidemiology can be investigated. using PCBaSe Sweden. [ABSTRACT FROM AUTHOR]

Alkylresorcinols (AR), phenolic lipids exclusively present in the outer parts of wheat and rye grains, have been proposed as conceltration biomarkers of whole-grain wheat and rye intake. A key feature of a good biomarker is high reproducibility, which indicates how accurately a single sample reflects the true mean biomarker concentration caused by a certain intake. In this study, the short- to medium-term reproducibility of plasma AR was determined using samples from a crossover intervention study, where men with prostate cancer (n = 17) were fed rye whole-grain/bran or refined wheat products for 6-wk periods. AR homologs C17:0 and C21:0 differed between the treatments (P < 0.001). The reproducibility determined by the intraclass correlation coefficient (ICC) was high (intervention period 1: ICC = 0.90 [95% Cl = 0.82-0.98), intervention period 2: ICC = 0.88 [95% Cl = 0.78-0.981]. The results show that a single fasting plasma sample could be used to estimate the mean plasma AR concentration during a 6-wk intervention period with constant intake at a precision of ± 20% (80% Cl). This suggests that the plasma AR concentration can be used as a reliable short- to medium-term biomarker for whole-grain wheat and rye under intervention conditions where intake is kept constant. [ABSTRACT FROM AUTHOR]

Background The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up. Methods From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided. Results During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [Cl] = 0.2 to 11.1%), for a relative risk of 0.65 (95% Cl = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% Cl = 0.2 to 13.2%), for a relative risk of 0.65 (95% Cl = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% Cl = 3.3 to 61.8; P < .001). Conclusion Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery. [ABSTRACT FROM AUTHOR]

Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of >100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer [ABSTRACT FROM AUTHOR]

Background Rates of long-term survival among patients with untreated localized prostate cancer are high. To avoid unnecessary treatment, tools are needed to identify the small proportion of patients who are destined to develop lethal prostate cancer. Methods To evaluate the accuracy of early changes in prostate-specific antigen (PSA) levels as predictors of prostate cancer outcome, we assessed serial measurements of PSA level among 267 men with localized prostate cancer in a Scandinavian cohort of men who were diagnosed between 1989 and 1999 and who were managed by watchful waiting. We then 1) fitted individual regression lines to the PSA values assessed for each patient during the first 2 years of follow-up by using three different models, 2) evaluated early PSA curve characteristics as determinants of the cumulative incidence of lethal prostate cancer and calculated hazard ratios for baseline PSA value and rate of change in PSA level to prostate cancer outcome, and 3) plotted time-dependent receiver operating characteristic (ROC) curves. All P values are two-sided. Results During complete follow-up for a mean of 8.5 years, 34 patients (13%) died from prostate cancer, and 18 (7%) developed metastases but were still alive at end of follow-up. In a log-linear model, both PSA value at base- line (P= .05) and the rate of PSA change (P<.001) were associated with the development of lethal prostate cancer. In the ROC analysis, however, the accuracy of classifying the disease as either indolent or destined to progress was low, regardless of the cut point chosen for initial PSA level or rate of change in PSA level. Conclusions Although baseline PSA value and rate of PSA change are prognostic factors for lethal prostate cancer, they are poor predictors of lethal prostate cancer among patients with localized prostate cancer who are managed by watchful waiting. [ABSTRACT FROM AUTHOR]

Objective. The Early Prostate Cancer (EPC) programme is evaluating the efficacy and tolerability of bicalutamide following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with localized (T1–2, N0/N×) or locally advanced (T3–4, any N; or any T, N&VeryThinSpace;+&VeryThinSpace;) non-metastatic prostate cancer. Herein we report the latest findings after a median follow-up period of 7.1 years from the Scandinavian Prostate Cancer Group (SPCG)-6 study, one of three trials in the EPC programme. Material and methods. A total of 1218 patients were randomized on a 1:1 basis to either bicalutamide 150 mg/day (n=607) or placebo (n=611) following standard care; 81.4% were followed conservatively (watchful waiting). The primary endpoints were objective progression-free survival (PFS) and overall survival (OS). Results. In patients with localized disease there was no significant difference in PFS [hazard ratio (HR) 0.85; 95% CI 0.69–1.06; p=0.15] and a trend towards decreased OS with bicalutamide plus standard care compared with standard care alone (HR 1.23; 95% CI 0.96–1.58; p=0.11). In patients with locally advanced disease, bicalutamide significantly improved PFS, reducing the risk of progression by 53% compared with standard care alone (HR 0.47; 95% CI 0.37–0.59; p<0.001). The median time to progression was 8.8 years for bicalutamide plus standard care and 7.1 years for standard care alone. There was a significant improvement in OS with bicalutamide plus standard care, with a reduction in the risk of death of 35% versus standard care alone (HR 0.65; 95% CI 0.50–0.85; p=0.001). Conclusion. This analysis of the SPCG-6 study showed that bicalutamide plus standard care offers significant PFS and OS benefits for patients with locally advanced disease, but not for those with localized disease. [ABSTRACT FROM AUTHOR]

Purpose: Adenocarcinoma of the prostate is the most common cancer among men in Western countries. Although the prognostic heterogeneity of prostate cancer is enormous, clinically insignificant aggressive prostate cancers cannot be reliably distinguished. Therefore, identifying prognostic factors is increasingly important, notably among men diagnosed with localized prostate cancer, because many of them may not require aggressive treatment. Materials and Methods: We analyzed a population based cohort of 253 men with early stage (T1a-b, Nx, M0) initially untreated prostate cancer diagnosed between 1977 and 1991, before PSA screening was available. Tissue samples were available for 240 patients diagnosed with transurethral resection. During complete followup through September 2003, standardized criteria were used to classify histopathological characteristics, progression and causes of death. Results: Higher Gleason grade, higher nuclear grade and larger tumor volume were independent predictors of death in prostate cancer with monotonous and statistically significant trends (p <0.05). In contrast, the level of Ki-67 – strongly correlated to Gleason score – was not an independent predictor of prostate cancer death. Given a Gleason score of 7 or greater, the probability of dying of prostate cancer was 29%. The corresponding predictive value for Gleason score 8 or greater was 48%. Conclusions: Although a high Gleason score is a determinant of prostate cancer death, its PPV is relatively low. Thus, further efforts in finding other or complementary indicators of prostate cancer outcome are needed. [Copyright &y& Elsevier]

Objective . To investigate the geographical variation in prostate cancer incidence in Sweden, in particular the incidences of screening-detected tumours and curative treatment of prostate cancer. Material and methods . Data were retrieved from the National Prostate Cancer Register of Sweden for all cases of prostate cancer diagnosed in the year 2000–01. There were a total of 14 376 cases of prostate cancer and the mean total annual age-adjusted incidence was 197/100 000 men. There were 3318 cases in tumour category T1c, i.e. non-palpable tumours diagnosed during work-up for an elevated serum level of prostate-specific antigen, 1006 of which (30%) were asymptomatic and detected at a health check-up. Results . The difference between the counties with the lowest and highest age-adjusted incidences per 100 000 men of total prostate cancer was almost twofold (128 vs 217). The corresponding variation in incidence of category T1c tumours was more than fourfold (13 vs 60); the difference in incidence of T1c tumours detected in asymptomatic men was up to 10-fold (2 vs 20); and there was more than a fourfold variation in incidence of curative treatment between counties (13 vs 67). Measured incidences were mostly highest in urban regions and in counties with university hospitals. Conclusion . There are large geographical variations in prostate cancer incidence and in the frequency of curative treatment for prostate cancer in Sweden and there appear to be large geographical variations in the uptake of prostate cancer screening. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation plays an important role in several human cancers and may be involved in the etiology of prostate cancer. Toll-like receptors (TLRs) are important in the innate immune response to pathogens and in cross-talk between innate immunity and adaptive immunity. Our previous finding of an association of TLR4 gene sequence variants and prostate cancer risk provides evidence for a role of TLRs in prostate cancer. In this study, we investigated whether sequence variants in the TLR6-TLR1-TLR10 gene cluster, residing within a 54-kb region on 4p14, were associated with prostate cancer risk. Methods: We selected 32 single-nucleotide polymorphisms (SNPs) covering these three genes and genotyped these SNPs in 96 control subjects from the Cancer Prostate in Sweden (CAPS) population-based prostate cancer case-control study. Five distinct haplotype blocks were inferred at this region, and we identified 17 haplotype-tagging SNPs (htSNPs) that could uniquely describe >95% of the haplotypes. These 17 htSNPs were then genotyped in the entire CAPS study population (1383 case subjects and 780 control subjects). Odds ratios of prostate cancer for the carriers of a variant allele versus those with the wild-type allele were estimated using unconditional logistic regression. Results: The allele frequencies of 11 of the 17 SNPs were statistically significantly different between case and control subjects (P = .04-.001), with odds ratios for variant allele carriers (homozygous or heterozygous) compared with wild-type allele carriers ranging from 1.20 (95% confidence interval [CI] = 1.00 to 1.43) to 1.38 (95% CI = 1.12 to 1.70). Phylogenetic tree analyses of common haplotypes identified a clade of two evolutionarily related haplotypes that are statistically significantly associated with prostate cancer risk. These two haplotypes contain all the risk alleles of these 11 associated SNPs. Conclusion: The observed multiple associated SNPs at the TLR6-TLR1-TLR10 gene cluster were dependent and suggest the presence of a founder prostate cancer risk variant on this haplotype background. The TLR6-TLR1-TLR10 gene cluster may play a role in prostate cancer risk, although further functional studies are needed to pinpoint the disease-associated variants in this gene cluster. [ABSTRACT FROM AUTHOR]

Objectives. To provide a descriptive review of the establishment of the National Prostate Cancer Register (NPCR) in Sweden, to present clinical characteristics at diagnosis and to calculate the relative survival of different risk groups after 5 years. Material and methods. Since 1998, data on all newly diagnosed prostate cancers, including TNM classification, grade of malignancy, prostate-specific antigen (PSA) level and treatment, have been prospectively collected. For the 35 223 patients diagnosed between 1998 and 2002, relative survival in different risk groups has been calculated. Results. Between 1998 and 2002, 96% of all prostate cancer cases diagnosed in Sweden were registered in the NPCR. The number of new cases increased from 6137 in 1998 to 7385 in 2002. The age-standardized rate rose in those aged <70 years, while it was stable, or possibly declining from 1999, in the older age groups. The proportion of T1c tumours increased from 14% to 28% of all recorded cases. The age-adjusted incidence of advanced tumours (M1 or PSA >100 ng/ml) decreased by 17%. The proportion of patients receiving curative treatment doubled. Patients with N1 or M1 disease or poorly differentiated tumours (G3 or Gleason score 8–10) had a markedly reduced relative 5-year survival rate. Conclusions. It is possible to establish a nationwide prostate cancer register including basic data for assessment of the disease in the whole of Sweden. The introduction of PSA screening has increased the detection of early prostate cancer in younger men and, to a lesser extent, decreased the incidence of advanced disease. The effect of these changes on mortality is obscure but the NPCR in Sweden will serve as an important tool in such evaluation. [ABSTRACT FROM AUTHOR]

Context Among men with early prostate cancer, the natural history without initial therapy determines the potential for survival benefit following radical local treatment. However, little is known about disease progression and mortality beyond 10 to 15 years of watchful waiting. Objective To examine the long-term natural history of untreated, early stage prostatic cancer. Design Population-based, cohort study with a mean observation period of 21 years. Setting Regionally well-defined catchment area in central Sweden (recruitment March 1977 through February 1984). Patients A consecutive sample of 223 patients (98% of all eligible) with early-stage (T0-T2 NX M0 classification), initially untreated prostatic cancer. Patients with tumor progression were hormonally treated (either by orchiectomy or estrogens) if they had symptoms. Main Outcome Measures Progression-free, cause-specific, and overall survival. Results After complete follow-up, 39 (17%) of all patients experienced generalized disease. Most cancers had an indolent course during the first 10 to 15 years. However, further follow-up from 15 (when 49 patients were still alive) to 20 years revealed a substantial decrease in cumulative progression-free survival (from 45.0% to 36.0%), survival without metastases (from 76.9% to 51.2%), and prostate cancer–specific survival (from 78.7% to 54.4%). The prostate cancer mortality rate increased from 15 per 1000 person-years (95% confidence interval, 10-21) during the first 15 years to 44 per 1000 person-years (95% confidence interval, 22-88) beyond 15 years of follow-up (P = .01). Conclusion Although most prostate cancers diagnosed at an early stage have an indolent course, local tumor progression and aggressive metastatic disease may develop in the long term. These findings would support early radical treatment, notably among patients with an estimated life expectancy exceeding 15 years. [ABSTRACT FROM AUTHOR]

Objective: The large increase in the incidence of prostate cancer is largely due to testing of serum levels of prostate-specific antigen (PSA). Little is known about how PSA testing is used in clinical practice outside of screening programmes. Essentially, PSA can be used in the health check-ups of men without symptoms as a form of non-systematic screening or in the work-up of symptomatic patients. The aim of this study was to investigate the cause of initiating a work-up leading to a diagnosis of prostate cancer, with emphasis on T1c tumours. Material and Methods: Data on the cause of initiation of work-up leading to a diagnosis of prostate cancer were retrieved from the National Prostate Cancer Registry for 6361 incident cases in tumour category T1c and local stages T2, T3 and T4 registered in Sweden in 2000. Results: For 1496 cases in tumour category T1c (non-palpable tumours detected during work-up of elevated PSA), the cause of PSA testing was health check-ups in 32% of cases, work-up of symptoms suspected to emanate from the prostate in 51% and other causes/not reported in 17%. For all stages combined, the cause of initiation of the diagnostic work-up was health check-ups in 18% of cases, symptoms in 68% and other causes/not reported in 14%. Conclusion: Non-systematic screening using PSA testing has been introduced in Sweden. However, prostate cancer is still most commonly diagnosed during the work-up of symptomatic patients. [ABSTRACT FROM AUTHOR]

Objective: The effectiveness of traditional follow-up programs and the intensive search for disease progression in men with prostate cancer have been questioned. The aims of this randomized multi-centre study were to evaluate medical safety, patient satisfaction and resource utilization in an on-demand follow-up by a specialist nurse compared with traditional follow-up by a urologist. Material and methods: Four hundred consecutively approached men with newly diagnosed or previously known prostate cancer in any stage at three hospitals in Sweden were randomized to follow-up in the nurse group (NG, 200 patients) or the urologist group (UG, 200 patients). In the NG, the nurse contacted the patient by phone every 6 months unless the patient himself initiated the contact. Patient satisfaction was evaluated twice a year via questionnaire. The questionnaire included the validated Hospital Anxiety and Depression Scale (HADS). The costs of all medical interventions and adverse events related to prostate cancer were calculated for all patients. Results: Medical safety, measured as complication frequency and lag time from symptoms to intervention, during the first 3 years of the observation period, was similar in the NG and the UG. The total number of interventions due to symptoms from prostate cancer was also similar in both groups. The analysis of accessibility and the HAD scale showed no significant differences between the groups. The mean outpatient cost (excluding pharmaceutical costs) per patient was lower in the NG compared to the UG, especially among patients without metastases at inclusion (37% lower cost). Conclusions: Our study indicates that men with prostate cancer can be safely followed up by a specialist nurse. The study results show that this alternative follow-up is cost-effective, especially in men without metastases. [ABSTRACT FROM AUTHOR]

Introduction: In 1996 registration of prostate cancer in four of the six Swedish regions was started to facilitate evaluation of geographical variations in incidence and treatment. Material and methods: For all cases of prostate cancer, personal identification number, tumour stage, tumour grade and primary treatment were registered. Results: In the four regions covered by the register, 3541 cases of prostate cancer were registered. Altogether there were 5795 cases of prostate cancer diagnosed in Sweden the same year. The age-standardized incidence varied from 89/100 000 to 169/100 000 among counties. The proportion of localized tumours correlated positively to the incidence (p < 0.05) and negatively to mean age at diagnosis (p < 0.01). There was also a significant positive correlation between the proportion of localized tumours and the percentage of patients given curative treatment. All registered variables showed large geographical variations, especially concerning percentage of T1c tumours, treatment of localized tumours and choice of palliative treatment. Conclusion: Diagnostic activity varied considerably among counties, resulting in large variation in age-standardized incidence. High incidence is associated with a larger proportion of localized tumours, which, in turn, is associated with early age at diagnosis. In counties where a policy of detecting tumours early is practised, curative treatment is also given more often. Treatment of localized tumours and preference for palliative treatment seem to depend on local traditions. The lack of cytological and histopathological standards makes geographical comparisons based on tumour grade impossible. [ABSTRACT FROM AUTHOR]

Presents a study, the objective of which is to describe the natural history of initially untreated early-stage prostate cancer. Key secondary objective to calculate long-term survival rates by stage, grade, and age at diagnosis; Design; Setting; Patients; Main outcome measures; Results; Conclusion.

We carried out a fine-mapping study in the HNF1B gene at 17q12 in two study populations and identified a second locus associated with prostate cancer risk, ∼26 kb centromeric to the first known locus (rs4430796); these loci are separated by a recombination hot spot. We confirmed the association with a SNP in the second locus (rs11649743) in five additional populations, with P = 1.7 × 10−9 for an allelic test of the seven studies combined. The association at each SNP remained significant after adjustment for the other SNP. [ABSTRACT FROM AUTHOR]

Background The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate. Methods A randomised, double-blind, parallel-group trial comparing bicalutamide 150 mg once daily with placebo in addition to standard care in patients with hormone-naïve, non-metastatic PCa. Kaplan–Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death). Findings A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised to receive bicalutamide in addition to their standard care and 611 to receive placebo. Median follow-up was 14.6 years. Overall, 866 (71.1%) patients died, 428 (70.5%) in the bicalutamide arm and 438 (71.7%) in the placebo arm, p = 0.87. Bicalutamide significantly improved OS in patient with locally advanced disease (hazard ratios (HR) = 0.77 (95% confidence interval (CI): 0.63–0.94, p = 0.01), regardless of baseline prostate-specific antigen (PSA), with a survival benefit which was apparent throughout the study period. In contrast, survival favoured randomisation to the placebo arm in patients with localised disease (HR = 1.19 (95% CI: 1.00–1.43), p = 0.056). However, a survival gain from bicalutamide therapy was present in patients with localised disease and a baseline PSA greater than 28 ng/mL at randomisation. In multivariate Cox proportional hazard model, only including patients managed on watchful waiting as their standard of care ( n = 991) OS depended on age, World Health Organisation (WHO) grade, baseline PSA, clinical stage and randomised treatment. Interpretation Throughout the 14.6 year follow-up period the addition of early bicalutamide to standard of care resulted in a significant OS benefit in patients with locally advanced PCa. In contrast, patients with localised PCa and low PSA derived no survival benefit from early bicalutamide. The optimal timing for initiating bicalutamide in non-metastatic PCa patients is dependent on disease stage and baseline PSA. [ABSTRACT FROM AUTHOR]

Abstract: Background: Studies enumerating the dynamics of physical and emotional symptoms following prostate cancer (PCa) treatment are needed to guide therapeutic strategy. Yet, overcoming patient selection forces is a formidable challenge for observational studies comparing treatment groups. Objective: To compare patterns of symptom burden and distress in men with localized PCa randomized to radical prostatectomy (RP) or watchful waiting (WW) and followed up longitudinally. Design, setting, and participants: The three largest, Swedish, randomization centers for the Scandinavian Prostate Cancer Group-4 trial conducted a longitudinal study to assess symptoms and distress from several psychological and physical domains by mailed questionnaire every 6 mo for 2 yr and then yearly through 8 yr of follow-up. Intervention: RP compared with WW. Outcome measurements and statistical analysis: A questionnaire was mailed at baseline and then repeatedly during follow-up with questions concerning physical and mental symptoms. Each analysis of quality of life was based on a dichotomization of the outcome (yes vs no) studied in a binomial response, generalized linear mixed model. Results and limitations: Of 347 randomized men, 272 completed at least five questionnaires during an 8-yr follow-up period. Almost all men reported that PCa negatively influenced daily activities and relationships. Health-related distress, worry, feeling low, and insomnia were consistently reported by approximately 30–40% in both groups. Men in the RP group consistently reported more leakage, impaired erection and libido, and fewer obstructive voiding symptoms. For men in the WW group, distress related to erectile symptoms increased gradually over time. Symptom burden and distress at baseline was predictive of long-term outlook. Conclusions: Cancer negatively influenced daily activities among almost all men in both treatment groups; health-related distress was common. Trade-offs exist between physiologic symptoms, highlighting the importance of tailored treatment decision-making. Men who are likely to experience profound long-term distress can be identified early in disease management. [Copyright &y& Elsevier]

Abstract: Background: Most localized prostate cancers are believed to have an indolent course. Within 15 yr of diagnosis, most deaths among men with prostate cancer (PCa) can be attributed to other competing causes. However, data from studies with extended follow-up are insufficient to determine appropriate treatment for men with localized disease. Objective: To investigate the long-term natural history of untreated, early-stage PCa. Design, setting, and participants: We conducted a population-based, prospective-cohort study using a consecutive sample of 223 patients with untreated, localized PCa from a regionally well-defined catchment area in central Sweden. All subjects were initially managed with observation. Androgen deprivation therapy was administered when symptomatic tumor progression occurred. Outcome measurements and statistical analysis: Based on >30 yr of follow-up, the main outcome measures were: progression-free, cause-specific, and overall survival, and rates of progression and mortality per 1000 person-years. Results and limitations: After 32 yr of follow-up, all but 3 (1%) of the 223 men had died. We observed 90 (41.4%) local progression events and 41 (18.4%) cases of progression to distant metastasis. In total, 38 (17%) men died of PCa. Cause-specific survival decreased between 15 and 20 yr, but stabilized with further follow-up. All nine men with Gleason grade 8–10 disease died within the first 10 yr of follow-up, five (55%) from PCa. Survival for men with well-differentiated, nonpalpable tumors declined slowly through 20 yr, and more rapidly between 20 and 25 yr (from 75.2% [95% confidence interval, 48.4–89.3] to 25% [95% confidence interval, 22.0–72.5]). It is unclear whether these data are relevant for tumors detected by elevated prostate-specific antigen levels. Conclusions: Although localized PCa most often has an indolent course, local progression and distant metastasis can develop over the long term, even among patients considered low risk at diagnosis. [Copyright &y& Elsevier]

Abstract: Background: Although there is randomized evidence that radical prostatectomy improves survival, there are few data on how benefit varies by baseline risk. Objective: We aimed to create a statistical model to calculate the decrease in risk of death associated with surgery for an individual patient, using stage, grade, prostate-specific antigen, and age as predictors. Design, setting, and participants: A total of 695 men with T1 or T2 prostate cancer participated in the Scandinavian Prostate Cancer Group 4 trial (SPCG-4). Intervention: Patients in SPCG-4 were randomized to radical prostatectomy or conservative management. Outcome measurements and statistical analysis: Competing risk models were created separately for the radical prostatectomy and the watchful waiting group, with the difference between model predictions constituting the estimated benefit for an individual patient. Results and limitations: Individualized predictions of surgery benefit varied widely depending on age and tumor characteristics. At 65 yr of age, the absolute 10-yr risk reduction in prostate cancer mortality attributable to radical prostatectomy ranged from 4.5% to 17.2% for low- versus high-risk patients. Little expected benefit was associated with surgery much beyond age 70. Only about a quarter of men had an individualized benefit within even 50% of the mean. A limitation is that estimates from SPCG-4 have to be applied cautiously to contemporary patients. Conclusions: Our model suggests that it is hard to justify surgery in patients with Gleason 6, T1 disease or in those patients much above 70 yr of age. Conversely, surgery seems unequivocally of benefit for patients who have Gleason 8, or Gleason 7, stage T2. For patients with Gleason 6 T2 and Gleason 7 T1, treatment is more of a judgment call, depending on patient preference and other clinical findings, such as the number of positive biopsy cores and comorbidities. [Copyright &y& Elsevier]

Summary: Background: For men with localised prostate cancer, surgery provides a survival benefit compared with watchful waiting. Treatments are associated with morbidity. Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from randomised settings. We report results for quality of life for men in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after a median follow-up of more than 12 years. Methods: All living Swedish and Finnish men (400 of 695) randomly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis. An additional 281 men were included in a population-based control group matched for region and age. Physical symptoms, symptom-induced stress, and self-assessed quality of life were evaluated with a study-specific questionnaire. Longitudinal data were available for 166 Swedish men who had answered quality-of-life questionnaires at an earlier timepoint. Findings: 182 (88%) of 208 men in the radical prostatectomy group, 167 (87%) of 192 men in the watchful-waiting group, and 214 (76%) of 281 men in the population-based control group answered the questionnaire. Men in SPCG-4 had a median follow-up of 12·2 years (range 7–17) and a median age of 77·0 years (range 61–88). High self-assessed quality of life was reported by 62 (35%) of 179 men allocated radical prostatectomy, 55 (34%) of 160 men assigned to watchful waiting, and 93 (45%) of 208 men in the control group. Anxiety was higher in the SPCG-4 groups (77 [43%] of 178 and 69 [43%] of 161 men) than in the control group (68 [33%] of 208 men; relative risk 1·42, 95% CI 1·07–1·88). Prevalence of erectile dysfunction was 84% (146 of 173 men) in the radical prostatectomy group, 80% (122 of 153) in the watchful-waiting group, and 46% (95 of 208) in the control group and prevalence of urinary leakage was 41% (71 of 173), 11% (18 of 164), and 3% (six of 209), respectively. Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting. In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart, 38 (45%) of 85 men allocated radical prostatectomy and 48 (60%) of 80 men allocated watchful waiting reported an increase in number of physical symptoms; 50 (61%) of 82 and 47 (64%) of 74 men, respectively, reported a reduction in quality of life. Interpretation: For men in SPCG-4, negative side-effects were common and added more stress than was reported in the control population. In the radical prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery. In the watchful-waiting group, side-effects can be caused by tumour progression. The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions. An understanding of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information. Funding: US National Institutes of Health; Swedish Cancer Society; Foundation in Memory of Johanna Hagstrand and Sigfrid Linnér. [Copyright &y& Elsevier]

Background: In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results. Methods: From October 1989 through February 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. Follow-up was complete through December 2009, with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death. Relative risks, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model. Results: During a median of 12.8 years, 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died (P=0.007). In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting, death was due to prostate cancer. This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7%, respectively (a difference of 6.1 percentage points; 95% confidence interval [CI], 0.2 to 12.0), and a relative risk with surgery of 0.62 (95% CI, 0.44 to 0.87; P=0.01). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men younger than 65 years of age. The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6 to 18.4). Conclusions: Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment. (Funded by the Swedish Cancer Society and the National Institutes of Health.) N Engl J Med 2011;364:1708-17. [ABSTRACT FROM AUTHOR]

Abstract: Background: Observational data indicate that retropubic radical prostatectomy (RRP) for prostate cancer (PCa) may induce inguinal hernia (IH) formation. Little is known about the influence of robot-assisted radical prostatectomy (RALP) on IH risk. Objective: To compare the incidence of IH after RRP and RALP to that of nonoperated patients with PCa and to a population control. Design, setting, and participants: We studied two groups. All 376 men included in the Scandinavian Prostate Cancer Group Study Number 4 constitute study group 1. Patients were randomly assigned RRP or watchful waiting (WW). The 1411 consecutive patients who underwent RRP or RALP at Karolinska University Hospital constitute study group 2. Men without PCa, matched for age and residence to each study group, constitute controls. Measurements: Postoperative IH incidence was detected through a validated questionnaire. The participation rates were 82.7% and 88.4% for study groups 1 and 2, respectively. Results and limitations: The Kaplan-Meier cumulative occurrence of IH development after 48 mo in study group 1 was 9.3%, 2.4%, and 0.9% for the RRP, the WW, and the control groups, respectively. There were statistically significant differences between the RRP group and the WW and control groups, but not between the last two. In study group 2 the cumulative risk of IH development at 48 mo was 12.2%, 5.8%, and 2.6% for the RRP, the RALP, and the control group, respectively. There were statistically significant differences between the RRP group and the RALP and control groups, but not between the last two. Conclusions: RRP for PCa leads to an increased risk of IH development. RALP may lower the risk as compared to open surgery. [ABSTRACT FROM AUTHOR]

Abstract: Background: Incidence of prostate cancer (PCa) has greatly increased in the Nordic region over the past two decades, following the advent of prostate-specific antigen (PSA) screening. Consequently, interpreting temporal trends in PCa has become difficult, and the impact of changes in exposure to causal factors is uncertain. Objective: To reveal geographic differences and temporal trends in PCa in the Nordic countries. Because the recorded incidence of PCa has been profoundly influenced by PSA screening, we focused our analyses primarily on PCa mortality. Design, setting, and participants: We analyzed national PCa incidence and mortality data from Denmark, Finland, Norway, and Sweden from 1965 to 2006 using the PC-NORDCAN software program and the online NORDCAN database. Measurements: Cumulative incidence and cumulative mortality from PCa were calculated for selected calendar years during four decades, along with age-standardized mortality rates. Incidence data in NORDCAN come from individual countries’ cancer registries, and mortality data come from national mortality registries. Results and limitations: From 1965 to 2006, 172 613 deaths from PCa were reported in the four Nordic countries. A substantial rise in incidence was observed across the region, with some geographic variation, since the late 1980s. In contrast, both disease-specific mortality rates and cumulative risk of PCa mortality lacked consistent temporal trends over the same period. Cumulative mortality from PCa ranged between 3.5% and 7.5% in the region over four decades, whereas cumulative incidence jumped from about 9% to >20%. Mortality has remained fairly constant among the countries, with a minimally lower risk in Finland. Conclusions: Unlike most malignancies, the occurrence of lethal PCa showed minimal geographic variation and lacked consistent temporal trends over four decades. These findings may guide our search for important causes of PCa, a malignancy with etiology that is still largely unknown. [Copyright &y& Elsevier]

Abstract: Background: Quality-of-life outcomes are important in the choice of treatment strategy for men with localized prostate cancer. Objective: To evaluate how follow-up time, number of physical symptoms, and presence of androgen deprivation affected quality of life among men randomized to radical prostatectomy or watchful waiting. Design, setting, and participants: The study group was composed of all 376 living men included in the Swedish part of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) [1] between January 1, 1989, and February 29, 1996. Quality-of-life data were collected after a mean follow-up time of 4.1 yr. Intervention: All patients were randomly assigned to radical prostatectomy or watchful waiting. Forty-five men were androgen deprived. Measurements: Data of specific symptoms, symptom-induced stress, sense of well-being, and self-assessed quality of life were obtained by means of a questionnaire. Psychological symptoms were assessed using seven-point visual digital scales. Results and limitations: In analyses stratified on the basis of the numbers of physical symptoms, anxiety and depressed mood were less common, and sense of well-being and self-assessed quality of life were better throughout in the radical prostatectomy group than in the watchful waiting group. As the number of physical symptoms increased, all psychological variables became worse and more prominent in the watchful waiting group. After a follow-up time of 6–8 yr, a significant decrease in quality of life (p =0.03) was seen in the watchful waiting group. Twenty-four percent of androgen-deprived patients assigned to watchful waiting reported high self-assessed quality of life compared with 60% in the radical prostatectomy group. Eighty-eight percent of patients had clinically detected tumors. Conclusions: Androgen deprivation negatively affected self-assessed quality of life in men assigned to watchful waiting. The number of physical symptoms was associated with the level of quality of life. Quality of life was lower with longer follow-up time in both groups and was statistically significant in the watchful waiting group (p =0.03). [Copyright &y& Elsevier]

Objectives: To report an exploratory subgroup analysis assessing the extent to which the overall benefit found in the Early Prostate Cancer program is dependent on lymph node status at randomization. The program is ongoing, and the overall survival data are immature. The first combined analysis of the bicalutamide (Casodex) Early Prostate Cancer program at 3 years'' median follow-up showed that bicalutamide, 150 mg once daily, plus standard care (radical prostatectomy, radiotherapy, or watchful waiting), significantly reduced the risk of objective progression and prostate-specific antigen (PSA) doubling in patients with localized/locally advanced prostate cancer.Methods: Men (n = 8113) with localized/locally advanced disease received bicalutamide 150 mg or placebo once daily, plus standard care. The time to event data (objective progression, PSA doubling) was analyzed by lymph node status at randomization.Results: Compared with standard care alone, bicalutamide significantly reduced the risk of objective progression, irrespective of lymph node status, with the most pronounced reduction in patients with N+ (hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.15 to 0.56) compared with those with N0 (HR 0.59; 95% CI 0.48 to 0.73) and Nx (HR 0.60; 95% CI 0.50 to 0.72) disease. The largest decrease in risk of PSA doubling with bicalutamide was observed in N+ disease (HR 0.16; 95% CI 0.09 to 0.29), with significantly reduced risks seen in N0 (HR 0.45; 95% CI 0.40 to 0.51) and Nx (HR 0.38; 95% CI 0.33 to 0.44) disease.Conclusions: The greatest reduction in the risk of objective progression and PSA doubling with bicalutamide was seen in patients with N+ disease. However, bicalutamide also provided a statistically significant benefit in those with N0 and Nx disease. [Copyright &y& Elsevier]

Background: In 2002, we reported the initial results of a trial comparing radical prostatectomy with watchful waiting in the management of early prostate cancer. After three more years of follow-up, we report estimated 10-year results. Methods: From October 1989 through February 1999, 695 men with early prostate cancer (mean age, 64.7 years) were randomly assigned to radical prostatectomy (347 men) or watchful waiting (348 men). The follow-up was complete through 2003, with blinded evaluation of the causes of death. The primary end point was death due to prostate cancer; the secondary end points were death from any cause, metastasis, and local progression. Results: During a median of 8.2 years of follow-up, 83 men in the surgery group and 106 men in the watchful-waiting group died (P=0.04). In 30 of the 347 men assigned to surgery (8.6 percent) and 50 of the 348 men assigned to watchful waiting (14.4 percent), death was due to prostate cancer. The difference in the cumulative incidence of death due to prostate cancer increased from 2.0 percentage points after 5 years to 5.3 percentage points after 10 years, for a relative risk of 0.56 (95 percent confidence interval, 0.36 to 0.88; P=0.01 by Gray's test). For distant metastasis, the corresponding increase was from 1.7 to 10.2 percentage points, for a relative risk in the surgery group of 0.60 (95 percent confidence interval, 0.42 to 0.86; P=0.004 by Gray's test), and for local progression, the increase was from 19.1 to 25.1 percentage points, for a relative risk of 0.33 (95 percent confidence interval, 0.25 to 0.44; P<0.001 by Gray's test). Conclusions: Radical prostatectomy reduces disease-specific mortality, overall mortality, and the risks of metastasis and local progression. The absolute reduction in the risk of death after 10 years is small, but the reductions in the risks of metastasis and local tumor progression are substantial. N Engl J Med 2005;352:1977-84. [ABSTRACT FROM AUTHOR]

Background: We evaluated symptoms and self-assessments of quality of life in men with localized prostate cancer who participated in a randomized comparison between radical prostatectomy and watchful waiting. Methods: Between 1989 and 1999, a group of Swedish urologists randomly assigned men with localized prostate cancer to radical prostatectomy or watchful waiting. In this follow-up study, we obtained information from 326 of 376 eligible men (87 percent) concerning certain symptoms, symptom-induced distress, well-being, and the subjective assessment of quality of life by means of a mailed questionnaire. Results: Erectile dysfunction (80 percent vs. 45 percent) and urinary leakage (49 percent vs. 21 percent) were more common after radical prostatectomy, whereas urinary obstruction (e.g., 28 percent vs. 44 percent for weak urinary stream) was less common. Bowel function, the prevalence of anxiety, the prevalence of depression, well-being, and the subjective quality of life were similar in the two groups. Conclusions: The assignment of patients to watchful waiting or radical prostatectomy entails different risks of erectile dysfunction, urinary leakage, and urinary obstruction, but on average, the choice has little if any influence on well-being or the subjective quality of life after a mean follow-up of four years. (N Engl J Med 2002;347:790-6.) [ABSTRACT FROM AUTHOR]